Mechanical activation of granulated copper slag (GCS) is carried out in the present study for the purposes of enhancing pozzolanic activity for the GCS. A vibration mill mills the GCS for 1, 2, and 3 h to produce samples with specific surface area of 0.67, 1.03 and 1.37 m²/g, respectively. The samples are used to replace 30% cement (PC) to get 3 PC-GCS binders. The hydration heat and compressive strength are measured for the binders and derivative thermogravimetric /thermogravimetric analysis (DTG/TGA), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM) are used to characterize the paste samples. It is shown that cumulative heat and compressive strength at different ages of hydration and curing, respectively, are higher for the binders blending the GCS milled for a longer time. The compressive strength after 90 d of curing for the binder with the longest milling time reaches 35.7 MPa, which is higher than the strength of other binders and close to the strength value of 39.3 MPa obtained by the PC pastes. The percentage of fixed lime by the binder pastes at 28 days is correlated with the degree of pozzolanic reaction and strength development. The percentage is higher for the binder blending the GCS with longer milling time and higher specific surface area. The pastes with binders blending the GCS of specific surface area of 0.67 and 1.37 m²/g fix lime of 15.20 and 21.15%, respectively. These results together with results from X-ray diffraction (XRD), FTIR, and SEM investigations demonstrate that the mechanical activation via vibratory milling is an effective method to enhance the pozzolanic activity and the extent for cement substitution by the GCS as a suitable supplementary cementitious material (SCM).